This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of my research is to identify mechanisms responsible for sperm differentiation using mice as a tool to understand normal development and aid in the treatment of human male infertility. Because human and mouse genomes are so similar, biological pathways are probably conserved between them. Mice with the repro27 chemically-induced mutation display male-specific infertility characterized by cell dealth in late meiosis and abnormal differentiatiion leading to abnormal sperm heads and tails. repro27 mice have a point mutation in the golgin subfamily A member 3 (Golga3) gene that inserts a premature stop codon. Protein expression analysis suggests that GOLGA3 protein is degraded. GOLGA3 is a Golgi complex protein implicated in protein trafficking of a certain proteins, apoptosis, and spermatogenesis. GOLGA3 is highly expressed in both somatic Sertoli cells and germ cells but its function is not known. The objective of this proposal is to understand GOLGA3's role in spermatogenesis by utilizing repro27 mutant mice known to carry a mutation in this gene. The central hypothesis is that repro27 mutant mice exhibit multiple spermatogenesis defects resulting from disrupted GOLGA3-dependent pathways. repro27 mice will be used to 1) conduct spermatogonial stem cell transplant experiments to determine if GOLGA3 function is germ cell specific;and 2) study the role of GOLGA3 in the testis at transcriptional and post-translational levels. Spermatogenesis in reciprocal stem cell transplant experiments will be used to determine cell type requirements. Validated protein targets and demonstrated protein interactions will dissect GOLGA3 pathways. Results will facilitate our understanding of spermatogenesis and may provide new clues and treatment options for human male infertility.